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Cardiopulmonary 2 > Pharmacology of the Autonomic Nervous System (ANS) > Flashcards

Pharmacology of the Autonomic Nervous System (ANS) Flashcards

1
Q

ANS subdivisions

A
  • Sympathetic (thoracolumbar, fight or flight)
  • Parasympathetic (craniosacral, rest and digest)
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2
Q

β1 on heart sinoatrial node

A

Increase in heart rate

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3
Q

M2 in heart sinoatrial node

A

Decrease in heart rate

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4
Q

β1 in heart atria

A

Increase in contractility and conduction velocity

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5
Q

M2 in heart atria

A

Decrease in contractility

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6
Q

β2 in lungs (tracheal and bronchial)

A

Relaxation

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7
Q

M2=M3 in lungs (bronchial and trachial)

A

Contraction

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8
Q

α1 in Eye (radial muscle “iris”)

A

Contraction (mydriasis)

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9
Q

M3, M2 in sphincter muscle (iris)

A

Contraction (miosis)

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10
Q

β2 in ciliary muscle of eye

A
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11
Q

M3, M2 for ciliary muscle of eyes

A

Contraction for near vision

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12
Q

Parasympathetic

A

Neurotransmitters: ACh
Receptors: nAChR, mAChR

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13
Q

Sympathetic

A

Neurotransmitters: NE > Epi (DA); ACh
Receptors: α, β, (D), nAChR, mAChR

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14
Q

Acetylcholine (cholinergic)

A
  • The major neurotransmitter of the parasympathetic nervous system
  • All preganglionic autonomic fibers
  • All postganglionic parasympathetic fibers
  • Few postganglionic sympathetic fibers (sweat glands)
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15
Q

Norepinephrine (adrenergic)

A
  • The major neurotransmitter of the sympathetic nervous system
  • The vast majority of postganglionic sympathetic fibers
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16
Q

Epinephrine (adrenergic)

A

•Synthesis only occurs in the adrenal medulla and in a few epinephrine-containing neuronal pathways in the brainstem

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17
Q

Dopamine (dopaminergic)

A
  • NE and Epi precursor
  • Acts on the CNS and renal vascular smooth muscle
18
Q

Co-neurotransmitters

A

ATP, neuropeptide Y, vasoactive intestinal peptide, substance P, others

19
Q

Junctional transmission

A

1) Synthesis of acetylcholine (ACh)
2) Storage
3) Release
4) Destruction

20
Q

nAChR (ionotropic)

A

Ion channels (fast) -Acetylcholine (Nicotine)

CNS
Autonomic ganglia (NN)
-Excitatory

Adrenal medula (NN)

-Release of
catecholamines

21
Q

mAChR (metabotropic)

A

G Protein coupled receptor - Acetylcholine (Muscarine)

CNS
Autonomic ganglia
Effector organs (cardiac and
smooth muscle, gland cells,
nerve terminals)

Sweat glands

Sweat secretion

22
Q

M2 on Heart, nerves, smooth muscle

A

GPCR, Gi/o

Inhibition of adenylyl cyclase (AC); ↓cAMP production, activation of K+
channels

23
Q

M3 on Glands, smooth muscle, endothelium

A

GPCR, **Gq/11 **

Activation of PLC; IP3, DAG cascade

24
Q

Junctional transmission

A
25
Q

Adrenergic nerve terminal

A

1) Synthesis
2) Storage
3) Release
4) Reuptake

26
Q

Termination of catecholamine signaling

A

Reuptake into nerve terminals

  • Major mechanism that terminates the actions of catecholamines
  • NET (norepinephrine transporter) and DAT (dopamine transporter)
  • After reuptake, catecholamines are stored in vesicles by the VMAT-2

Metabolism of catecholamines (2 main enzymes)
•Monoamine oxidase (MAO)
•Catechol-O-methyltransferase (COMT)

\*In contrast to cholinergic signaling, termination of catecholamine action by
degradative enzymes (i.e., AChE) is nonexistent in adrenergic signaling
27
Q

α-receptors

A
  • GPCR
  • Pre- and postjunctional
  • Two major subtypes (α1,α2)
28
Q

β-receptors

A
  • GPCR
  • Pre- and postjunctional
  • Three major subtypes (β1, β2, β3)
29
Q

Adrenergic signaling

A

Na+-dependent tyrosine transporter
•Transports tyrosine into the nerve terminal

Vesicular monoamine transporter (VMAT-2)
•Transports NE, Epi, DA, and serotonin into vesicles (promiscuous)
Release upon action potential and Ca2+ influx

NE transporter (NET)

_*Cocaine inhibits this giving sympathetic effects_
•Imports NE into the nerve terminal
•DAT imports DA into the nerve terminal

30
Q

Alpha1 adrenergic receptor

A

Gq

↑phospholipase C, IP3 and DAG, intracellular Ca2+

Epi ≥ NE >> Isoproterenol
Phenylephrine

smooth muscle - contraction

Intestinal smooth muscle - hyperpolarization and relaxation

Heart - Increased contractile force; arrhythmias

31
Q

Alpha2 adrenergic receptor

A

Gi, Go

↓adenylyl cyclase
↓cAMP

Epi ≥ NE >> Iso
Clonidine

Vascular smooth muscle

Contraction

32
Q

Beta1 adrenergic receptor

A

Gs
↑adenylyl cyclase, cAMP, Ltype
Ca2+ channel opening

Iso > Epi = NE
Dobutamine

Juxtaglomerular cells

Increased renin secretion

Heart

Increased force and rate of contraction and
AV nodal conduction velocity

33
Q

Beta2 adrenergic receptor

A

Gs
↑adenylyl cyclase, cAMP, Ltype
Ca2+ channel opening

Iso > Epi >> NE
Terbutamine

Smooth muscle (vascular, bronchial, GI, GU)

Relaxation

34
Q

Beta3 adrenergic receptor

A

Gs
↑adenylyl cyclase, cAMP, Ltype
Ca2+ channel opening

Iso = NE > Epi

Adipose tissue

Lipolysis

35
Q

Sympathomimetic agents: drugs that mimic or enhance α-and β-receptor stimulation

A

Epinephrine (α1 = α2, β1 = β2)

Norepinephrine (α1 = α2, β1 >> β2)

Isoproterenol (β1 = β2 >>>> α)

36
Q

Primary Tissue Locations of Adrenergic Receptor Subtypes

A
37
Q

Rules of thumb for smooth muscle and autonomic receptors

A

Alpha-1 (α1) receptors
•Stimulate contraction of all smooth muscle
•Vascular smooth muscle – vasoconstriction

Beta-2 (β2) receptors
•Relax smooth muscle – vasodilation

Muscarinic receptors
•Contract smooth muscle (different intracellular signal than α1 receptors)

(Depends on relative receptor density.)

38
Q

Response of blood vessels to autonomic
nerve impulses

A

•Blood vessels are innervated by adrenergic receptors, which cause vessel
constriction when activated (sympathetic)

  • Smooth muscle of blood vessels is NOT innervated by parasympathetic neurons
  • Neither mAChRs nor nAChRs are found on smooth muscle of blood vessels

•Blood vessels relax in response to parasympathetic release of ACh as long as the
epithelium is intact

•Apparent discrepancy – ACh & muscarinic agonists given IV cause vasodilation due to
release of nitric oxide (NO)

39
Q

mAChRs, EDRF (NO), and vessel relaxation

A

Activation of mAChRs on epithelial cells causes production and release of
endothelium-derived relaxing factor (EDRF), also known as nitric oxide (NO)
Stimulation of NO release can occur from ACh, vasoactive
products, and physical stimuli.

Nitroglycerin is similar to the NO as it
helps open up the smooth
muscle vessels.

40
Q

Adrenal medulla

A

•Sympathetic innervation

  • Epi and NE release is triggered by the release of ACh from the preganglionic fibers
  • ACh binds to NNAChRs (on chromaffin cells) and produce a localized depolarization

•Release is approximately:
80% Epi
20% NE

41
Q

Baroreceptor reflex as an
example of compensatory
changes in the ANS

A

Balance between sympathetic and
parasympathetic. When we’re laying down
and everything is vasodilated. Blood
pressure is low when relaxing. When we get
up the blood pressure goes up.

42
Q
A

Cardiopulmonary 2 (5 decks)

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